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Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis

Evidence shows that chaperone-mediated autophagy (CMA) is involved in cancer cell pathogenesis and progression. However, the potential role of CMA in breast cancer angiogenesis remains unknown. We first manipulated CMA activity by knockdown and overexpressing of lysosome-associated membrane protein...

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Autores principales: Chen, Rui, Li, Peng, Fu, Yan, Wu, Zongyao, Xu, Lijun, Wang, Junhua, Chen, Sha, Yang, Mingzhen, Peng, Bingjie, Yang, Yao, Zhang, Hongwei, Han, Qi, Li, Shuhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10010525/
https://www.ncbi.nlm.nih.gov/pubmed/36913368
http://dx.doi.org/10.1371/journal.pone.0281577
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author Chen, Rui
Li, Peng
Fu, Yan
Wu, Zongyao
Xu, Lijun
Wang, Junhua
Chen, Sha
Yang, Mingzhen
Peng, Bingjie
Yang, Yao
Zhang, Hongwei
Han, Qi
Li, Shuhui
author_facet Chen, Rui
Li, Peng
Fu, Yan
Wu, Zongyao
Xu, Lijun
Wang, Junhua
Chen, Sha
Yang, Mingzhen
Peng, Bingjie
Yang, Yao
Zhang, Hongwei
Han, Qi
Li, Shuhui
author_sort Chen, Rui
collection PubMed
description Evidence shows that chaperone-mediated autophagy (CMA) is involved in cancer cell pathogenesis and progression. However, the potential role of CMA in breast cancer angiogenesis remains unknown. We first manipulated CMA activity by knockdown and overexpressing of lysosome-associated membrane protein type 2A (LAMP2A) in MDA-MB-231, MDA-MB-436, T47D and MCF7 cells. We found that the tube formation, migration and proliferation abilities of human umbilical vein endothelial cells (HUVECs) were inhibited after cocultured with tumor-conditioned medium from breast cancer cells of LAMP2A knockdown. While the above changes were promoted after cocultured with tumor-conditioned medium from breast cancer cells of LAMP2A overexpression. Moreover, we found that CMA could promote VEGFA expression in breast cancer cells and in xenograft model through upregulating lactate production. Finally, we found that lactate regulation in breast cancer cells is hexokinase 2 (HK2) dependent, and knockdown of HK2 can significantly reduce the ability of CMA-mediated tube formation capacity of HUVECs. Collectively, these results indicate that CMA could promote breast cancer angiogenesis via regulation of HK2-dependent aerobic glycolysis, which may serve as an attractive target for breast cancer therapies.
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spelling pubmed-100105252023-03-14 Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis Chen, Rui Li, Peng Fu, Yan Wu, Zongyao Xu, Lijun Wang, Junhua Chen, Sha Yang, Mingzhen Peng, Bingjie Yang, Yao Zhang, Hongwei Han, Qi Li, Shuhui PLoS One Research Article Evidence shows that chaperone-mediated autophagy (CMA) is involved in cancer cell pathogenesis and progression. However, the potential role of CMA in breast cancer angiogenesis remains unknown. We first manipulated CMA activity by knockdown and overexpressing of lysosome-associated membrane protein type 2A (LAMP2A) in MDA-MB-231, MDA-MB-436, T47D and MCF7 cells. We found that the tube formation, migration and proliferation abilities of human umbilical vein endothelial cells (HUVECs) were inhibited after cocultured with tumor-conditioned medium from breast cancer cells of LAMP2A knockdown. While the above changes were promoted after cocultured with tumor-conditioned medium from breast cancer cells of LAMP2A overexpression. Moreover, we found that CMA could promote VEGFA expression in breast cancer cells and in xenograft model through upregulating lactate production. Finally, we found that lactate regulation in breast cancer cells is hexokinase 2 (HK2) dependent, and knockdown of HK2 can significantly reduce the ability of CMA-mediated tube formation capacity of HUVECs. Collectively, these results indicate that CMA could promote breast cancer angiogenesis via regulation of HK2-dependent aerobic glycolysis, which may serve as an attractive target for breast cancer therapies. Public Library of Science 2023-03-13 /pmc/articles/PMC10010525/ /pubmed/36913368 http://dx.doi.org/10.1371/journal.pone.0281577 Text en © 2023 Chen et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chen, Rui
Li, Peng
Fu, Yan
Wu, Zongyao
Xu, Lijun
Wang, Junhua
Chen, Sha
Yang, Mingzhen
Peng, Bingjie
Yang, Yao
Zhang, Hongwei
Han, Qi
Li, Shuhui
Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis
title Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis
title_full Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis
title_fullStr Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis
title_full_unstemmed Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis
title_short Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis
title_sort chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10010525/
https://www.ncbi.nlm.nih.gov/pubmed/36913368
http://dx.doi.org/10.1371/journal.pone.0281577
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